Summary: Lipooligosaccharide (LOS) is one of the major surface antigens of Neisseria meningitidis. It can be serologically divided into 12 immunotypes. Epidemiological studies have revealed that the L3,7 immunotype is the most common immunotype among serogroups B and C organisms causing disease, the predominant serogroups of meningococcal disease in the U. S. and Europe. We need to know the structure of LOS and its biological implications in the development of detoxified LOS-protein conjugate as potential vaccine for the prevention of group B disease, which currently has no licensed vaccines. The L3,7 LOS possesses the immunotype epitope and also other epitopes including the lacto-N-neotetraose (LNnT) structure, a precursor of ABO major blood group antigens such as paragloboside (LNnT-ceramide) on human cells and tissues. In group B and C organisms, the LNnT epitope in the alpha chain extending out from the heptose (I) in the inner core of LOS is often sialylated. It has been shown that sialylation of LOS enhances N. meningitidis to resist killing by normal human serum. Thus, we studied the effect of LOS receptor on the LOS sialylation. Our study has shown that the length of alpha chain influenced sialylation of N. meningitidis LOS in vitro and in vivo. The alpha chain required a terminal Gal and a trisaccharide or higher oligosaccharide to serve as acceptor for sialylation. The disaccharide, lactose (Gal1-4Glc), in the alpha chain of immunotype L8 LOS could not function as an acceptor for the sialyltransferase probably due to steric hindrance imposed by the second neighboring heptose (II) in the inner core with a phosphorylethanolamine attachment. Lack of LOS sialylation in N. meningitidis expressing the L8 phenotype may result in its sensitivity to serum bactericidal activity.